%0 Journal Article
%A Korshunov, Andrey
%A Okonechnikov, Konstantin
%A Stichel, Damian
%A Schrimpf, Daniel
%A Delaidelli, Alberto
%A Tonn, Svenja
%A Mynarek, Martin
%A Sievers, Philipp
%A Sahm, Felix
%A Jones, David
%A von Deimling, Andreas
%A Pfister, Stefan
%A Kool, Marcel
%T Gene expression profiling of Group 3 medulloblastomas defines a clinically tractable stratification based on KIRREL2 expression.
%J Acta neuropathologica
%V 144
%@ 0001-6322
%C Heidelberg
%I Springer
%M DKFZ-2022-01396
%P 339–352
%D 2022
%Z #EA:B300#LA:B062# / 144, pages 339–352 (2022)
%X Medulloblastomas (MB) molecularly designated as Group 3 (Grp 3) MB represent a more clinically aggressive tumor variant which, as a group, displays heterogeneous molecular characteristics and disease outcomes. Reliable risk stratification of Grp 3 MB would allow for appropriate assignment of patients to aggressive treatment protocols and, vice versa, for sparing adverse effects of high-dose radio-chemotherapy in patients with standard or low-risk tumors. Here we performed RNA-based analysis on an international cohort of 179 molecularly designated Grp 3 MB treated with HIT protocols. We analyzed the clinical significance of differentially expressed genes, thereby developing optimal prognostic subdivision of this MB molecular group. We compared the transcriptome profiles of two Grp 3 MB subsets with various outcomes (76 died within the first 60 months vs. 103 survived this period) and identified 224 differentially expressed genes (DEG) between these two clinical groups (Limma R algorithm, adjusted p-value < 0.05). We selected the top six DEG overexpressed in the unfavorable cohort for further survival analysis and found that expression of all six genes strongly correlated with poor outcomes. However, only high expression of KIRREL2 was identified as an independent molecular prognostic indicator of poor patients' survival. Based on clinical and molecular patterns, four risk categories were outlined for Grp 3 MB patients: i. low-risk: M0-1/MYC non-amplified/KIRREL2 low (n = 48; 5-year OS-95
%K Expression (Other)
%K Group 3 (Other)
%K KIRREL2 (Other)
%K Medulloblastoma (Other)
%K Prognosis (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35771282
%R 10.1007/s00401-022-02460-1
%U https://inrepo02.dkfz.de/record/180534